Accumulating interest has emerged in exploring the toxicity profiles of the combination strategy of radiotherapy (RT) and immune checkpoint inhibitors (ICIs). Much remains unknown regarding safety and the potential increased risk of toxicity of a combined treatment. ICI prolongs survival but can induce immune-related adverse events as well. To increase awareness of adverse effect and support immediate and successful management, we go over the literature on the safety of RT combined immunotherapy strategy. Representative evidence relevant to RT combined with ICI in the brain, lung, head and neck, and pelvic malignance was reviewed respectively. Given radiation doses and fractionation, the irradiated volume, the timing of RT, and ICI would significantly affect the safety and efficiency of ICI+RT combination therapy, and no consensus had been reached about how to arrange RT delivery in the combined contexture, we went over the available literature and tried to address these challenges including the timing of RT, optimal dose and fractionations, RT target and target volume, and potential biomarkers to predict toxicity. We found even though RT+ICI combination therapy might augment toxicities, the majority of patients experienced grade 4 or 5 AE are relatively rare and no significant difference could be found between combination group and monotherapy group. Sometimes the acute toxicity with ICI is much less predictable and often life threatening and in some can give rise to permanent effects. Clinicians across disciplines should be aware of these uncommon lethal complications induced by ICI+RT. Early recognition is the key to successful treatment, reversibility of organ dysfunction, and in some cases even prevention of fatal outcome. If recognized early, managed properly, and no fatal AE occurs, the development of irAE indicates a good prognosis. It should be noted that nothing is known about potential late effects because very few studies have 5-year follow-up.

中文翻译：

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放射治疗联合免疫治疗策略的安全性和潜在增加的毒性风险

人们越来越关注探索放疗 (RT) 和免疫检查点抑制剂 (ICI) 联合策略的毒性特征。关于联合治疗的安全性和潜在增加的毒性风险，还有很多未知数。ICI 可延长生存期，但也会诱发免疫相关的不良事件。为了提高对不良反应的认识并支持立即和成功的管理，我们查阅了有关 RT 联合免疫治疗策略安全性的文献。分别回顾了在脑、肺、头颈和盆腔恶性肿瘤中与 RT 联合 ICI 相关的代表性证据。考虑到辐射剂量和分割、照射体积、RT 和 ICI 的时间将显着影响 ICI + RT 联合治疗的安全性和效率，并且对于如何在组合环境中安排放疗尚未达成共识，我们查阅了可用的文献并试图解决这些挑战，包括放疗的时间、最佳剂量和分割、放疗目标和目标体积以及潜在的生物标志物预测毒性。我们发现，尽管 RT+ICI 联合治疗可能会增加毒性，但大多数患者出现 4 级或 5 级 AE 的情况相对较少，联合治疗组和单一治疗组之间没有显着差异。有时，ICI 的急性毒性难以预测，通常会危及生命，而在某些情况下，可能会产生永久性影响。跨学科的临床医生应该意识到 ICI+RT 引起的这些罕见的致命并发症。早期识别是成功治疗的关键，器官功能障碍的可逆性，在某些情况下甚至可以预防致命后果。如果及早发现、管理得当并且没有发生致命性 AE，则 irAE 的发展预示着良好的预后。应该指出的是，对于潜在的迟发效应一无所知，因为很少有研究有 5 年的随访。